Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.

Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.

Objective:To establish a new method and platform for screening, identifying, and exploring a new strategy for anti-hepatitis B immunotherapy based on hepatitis B virus (HBV)-specific TCR.Methods:Peripheral blood mononuclear cells were isolated from patients with acute hepatitis B. CD3 +CD8 +CD137 +T single cells were sorted out after stimulation with the HBsAg peptide library. The α and β chains in TCRs of single cells were amplified by PCR. TCR double-chain pairing and lentiviral packaging were performed through high-throughput sequencing. Re-infected Jurkat-76-NFAT-GFP cells and the cell lines stably expressing TCR were screened. HBsAg peptide library and immortalized B lymphocytes co-cultured with J76N-TCR were used to screen HBsAg-specific TCRs. K562 cell lines stably expressing HLA-A*24:02 were established to determine epitope peptide by screening A*24:02-restricted TCR. The screened TCRs were replaced with mouse C regions and packaged with lentiviruses. Functional validation was performed on healthy human CD4 +T and CD8 +T lymphocytes following infection. Results:Stable TCR-expressing cell lines were successfully prepared based on single-cell TCRαβ double-chain amplification and pairing technology. Twenty-one TCRs were screened using immortalized B lymphocytes, resulting in nine possible HLA-A*24:02-restricted HBsAg-specific TCRs. Further screening with K562-A2402 resulted in six A*24:02-restricted HBsAg-specific TCRs with identically recognized epitope peptide. The functional determination of the two TCR clones revealed their specific recognition function for target cells expressing HBsAg.Conclusion:HLA-A*24:02-restricted HBsAg-specific TCR with recognition function for target cells expressing HBsAg was successfully obtained based on the new experimental technology system, laying an important foundation for further exploration of antiviral immunotherapy based on HBV-specific TCR.

AIM:To investigate the impact of core 1 β3-galactosyltransferase-specific molecular chaperone(COSMC)on the stem cell-like properties of gastric adenocarcinoma cells,and to elucidate its underlying mechanism.METHODS:GEPIA(Gene Expression Profiling Interactive Analysis),TIMER(Tumor IMmune Estimation Resource),Wei Sheng Xin platform,UALCAN(University of Alabama at Birmingham Cancer Data Analysis Portal)and UCSC(Uni-versity of California,Santa Cruz)Xena databases were employed to analyze COSMC expression levels across various carci-noma types.The COSMC expression in gastric cancer tissues and cell lines was evaluated using Western blot analysis.Transfection of small interfering RNA was used to knock down COSMC in MKN-45 cell line.In vitro experiments were con-ducted to explore the relationship between the COSMC expression and the stem cell-like properties of gastric cancer.The qPCR,sphere formation assay,soft agar colony formation assay and CCK-8 assay were used to evaluate the effect of COSMC on the stem cell-like properties of gastric cancer cells.Tn+and Tn-cells were isolated using Vicia villosa lectin(VVL)-conjugated immunomagnetic beads to investigate the influence of Tn structure on the stem cell-like characteristics of gastric cancer cells.Finally,the effect of COSMC knockdown on the mitogen-activated protein kinase(MAPK)signal-ing pathway was evaluated by Western blot analysis.RESULTS:(1)The COSMC exhibited differential expression across pancarcinoma,gastric cancer tissues and gastric cancer cell lines,with elevated expression levels in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and gastric epithelial cell line.(2)Knockdown of COSMC sig-nificantly down-regulated the mRNA levels of stem cell markers NANOG,OCT-4 and CD44 in gastric cancer cells,re-duced the efficiency of soft agar colony formation and sphere formation,and increased the sensitivity of the cells to 5-fluo-rouracil(5-FU).(3)The efficiency of tumor sphere formation and soft agar colony formation in Tn-cells,and the resis-tance to 5-FU were significantly higher than those in Tn+cells.(4)Knockdown of COSMC decreased the protein levels of MAPK signaling pathway-related molecules,including c-Jun N-terminal kinase(JNK),p38 and phosphorylated extracel-lular signal-regulated kinase(p-ERK).CONCLUSION:The COSMC has the potential to enhance the stem cell-like properties of gastric cancer cells,which was likely mediated through the activation of the MAPK signaling pathway.

Objective:To investigate the sero-conversion rate of HIV antibody and influencing factors in cross-border couples in Dehong Dai and Jingpo Autonomous Prefecture(Dehong).Methods:A cohort design was used to recruit HIV-negative people in cross-border couples in Dehong in 2017. Follow-up was conducted in 2023, and questionnaire survey and HIV test were carried out to calculate the sero-conversion rate of HIV antibody. Univariate and multivariate logistic regression models were used to analyze the influence factors for HIV infections.Results:A total of 36 278 HIV-negative persons in cross-border couples were included in the 2017 baseline survey, of whom 22 438 (61.9%) were tested in follow-up in 2023. The sero-conversion rate between 2017 and 2023 was 0.51% (115/22 438). Multivariate logistic regression analysis showed that length of marriage <6 years, Jingpo ethnic group, education level of primary school or below, drug use, illegal marriage and HIV infected spouse were the risk factors of HIV infection in male spouses, and length of marriage <6 years, Jingpo ethnic group, illegal marriage and HIV infected spouse were the risk factors in female spouses.Conclusions:The sero-conversion rate of HIV antibody in cross-border couples in Dehong was relatively high. HIV infection was mainly caused by secondary transmission in the couples, and men might also be infected through drug use. It is necessary to strengthen the registration and management of cross-border couples, especially the couples with discordant HIV infection status, and the intervention in drug users to reduce the risk for secondary transmission of HIV in the cross-border couples.

AIM:To investigate the impact of core 1 β3-galactosyltransferase-specific molecular chaperone(COSMC)on the stem cell-like properties of gastric adenocarcinoma cells,and to elucidate its underlying mechanism.METHODS:GEPIA(Gene Expression Profiling Interactive Analysis),TIMER(Tumor IMmune Estimation Resource),Wei Sheng Xin platform,UALCAN(University of Alabama at Birmingham Cancer Data Analysis Portal)and UCSC(Uni-versity of California,Santa Cruz)Xena databases were employed to analyze COSMC expression levels across various carci-noma types.The COSMC expression in gastric cancer tissues and cell lines was evaluated using Western blot analysis.Transfection of small interfering RNA was used to knock down COSMC in MKN-45 cell line.In vitro experiments were con-ducted to explore the relationship between the COSMC expression and the stem cell-like properties of gastric cancer.The qPCR,sphere formation assay,soft agar colony formation assay and CCK-8 assay were used to evaluate the effect of COSMC on the stem cell-like properties of gastric cancer cells.Tn+and Tn-cells were isolated using Vicia villosa lectin(VVL)-conjugated immunomagnetic beads to investigate the influence of Tn structure on the stem cell-like characteristics of gastric cancer cells.Finally,the effect of COSMC knockdown on the mitogen-activated protein kinase(MAPK)signal-ing pathway was evaluated by Western blot analysis.RESULTS:(1)The COSMC exhibited differential expression across pancarcinoma,gastric cancer tissues and gastric cancer cell lines,with elevated expression levels in gastric cancer tissues and gastric cancer cell lines compared with normal tissues and gastric epithelial cell line.(2)Knockdown of COSMC sig-nificantly down-regulated the mRNA levels of stem cell markers NANOG,OCT-4 and CD44 in gastric cancer cells,re-duced the efficiency of soft agar colony formation and sphere formation,and increased the sensitivity of the cells to 5-fluo-rouracil(5-FU).(3)The efficiency of tumor sphere formation and soft agar colony formation in Tn-cells,and the resis-tance to 5-FU were significantly higher than those in Tn+cells.(4)Knockdown of COSMC decreased the protein levels of MAPK signaling pathway-related molecules,including c-Jun N-terminal kinase(JNK),p38 and phosphorylated extracel-lular signal-regulated kinase(p-ERK).CONCLUSION:The COSMC has the potential to enhance the stem cell-like properties of gastric cancer cells,which was likely mediated through the activation of the MAPK signaling pathway.

Objective:To establish a new method and platform for screening, identifying, and exploring a new strategy for anti-hepatitis B immunotherapy based on hepatitis B virus (HBV)-specific TCR.Methods:Peripheral blood mononuclear cells were isolated from patients with acute hepatitis B. CD3 +CD8 +CD137 +T single cells were sorted out after stimulation with the HBsAg peptide library. The α and β chains in TCRs of single cells were amplified by PCR. TCR double-chain pairing and lentiviral packaging were performed through high-throughput sequencing. Re-infected Jurkat-76-NFAT-GFP cells and the cell lines stably expressing TCR were screened. HBsAg peptide library and immortalized B lymphocytes co-cultured with J76N-TCR were used to screen HBsAg-specific TCRs. K562 cell lines stably expressing HLA-A*24:02 were established to determine epitope peptide by screening A*24:02-restricted TCR. The screened TCRs were replaced with mouse C regions and packaged with lentiviruses. Functional validation was performed on healthy human CD4 +T and CD8 +T lymphocytes following infection. Results:Stable TCR-expressing cell lines were successfully prepared based on single-cell TCRαβ double-chain amplification and pairing technology. Twenty-one TCRs were screened using immortalized B lymphocytes, resulting in nine possible HLA-A*24:02-restricted HBsAg-specific TCRs. Further screening with K562-A2402 resulted in six A*24:02-restricted HBsAg-specific TCRs with identically recognized epitope peptide. The functional determination of the two TCR clones revealed their specific recognition function for target cells expressing HBsAg.Conclusion:HLA-A*24:02-restricted HBsAg-specific TCR with recognition function for target cells expressing HBsAg was successfully obtained based on the new experimental technology system, laying an important foundation for further exploration of antiviral immunotherapy based on HBV-specific TCR.

ObjectiveTo explore the prevalence and influencing factors of multimorbidity among the HIV-infected individuals receiving anti-viral therapy (ART) in Dehong Prefecture of Yunnan Province, so as to provide a reference for the long-term follow-up management of HIV-infected patients and the comprehensive prevention and treatment of chronic diseases. MethodsA cross-sectional study was conducted to investigate the multimorbidity burden among the HIV-infected adults receiving ART in Dehong Prefecture from January to July 2021 and a self-designed questionnaire was used to analyze relevant disease indicators. Multivariate logistic regression analysis was used to investigate the influencing factors of multimorbidity among the HIV-infected individuals. ResultsA total of 3 946 HIV-infected individuals receiving ART were enrolled in this study, of which 63.7% aged ≤50 years, with a male to female ratio of 1.1∶1. Among the 3 946 cases, 825 of them had ≥2 comorbidities, with a co-prevalence rate of 20.9% (95%CI:19.6%‒22.2%), and the main comorbidities were dyslipidemia, diabetes, and hypertension. Multivariate logistic regression analysis showed that 40≤ aged <50 years (aOR=1.86, 95%CI: 1.45‒2.40, P<0.001), 50≤ aged ≤85 years (aOR=3.75, 95%CI: 2.93‒4.80, P<0.001), Dai nationality (aOR=1.21, 95%CI: 1.01‒1.47, P=0.043), BMI≥24.0 kg∙m^-2 (aOR=1.79, 95%CI: 1.49‒2.14, P<0.001), 10.0≤ with ART duration for <12.5 years (aOR=1.49, 95%CI: 1.05‒2.12, P=0.024), with ART duration for ≥12.5 years (aOR=1.50, 95%CI: 1.05‒2.15, P=0.026), use of second-line HIV therapy (aOR=1.43, 95%CI: 1.19‒1.70, P<0.001) and other therapy options (aOR=3.16, 95%CI: 2.17‒4.61, P<0.001) were positively correlated with multimorbidity. ConclusionThe prevalence of multimorbidity among the HIV-infected individuals receiving ART in Dehong Prefecture is high, which is associated with the advancing age and prolonged treatment time, particularly with a significant burden of dyslipidemia, diabetes, and hypertension. Comprehensive surveillance and targeted management of comorbidities, along with ART follow-up, need to be strengthened in the future.

Objective To compare the changes of the Chinese Materia Medica resources(CMMR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2011-2022).Methods Using new techniques,after field investigation,collection and identification of the specimens of the animals,plants and minerals.The data of the CMMR in Sichuan found in the 4th CMMRI were analysed and compared with the data of 3rd CMMRI.Results ①9055 species of CMMR were found in Sichuan during the 4th CMMRI,including 8272 species of medicinal plants,745 species of medicinal animals and 38 species of medicinal minerals.Compared with the 3rd CMMRI,the number of CMMR found in Sichuan have greatly increased.The number of medicinal plants increased 5018 species,the number of medicinal animals increased 637 species and the number of medicinal minerals increased 5 species,too.②The medicinal plants is the main part of the CMMR,and the higher plants(7774 species)has the absolute advantage of the CMMR.The top 20 families which have plenty of plant species include Compositae,Rosaceae,Leguminosae,Ranunculaceae,etc.③ Based on the data of the CMMR of the 183 counties in Sichuan,the reserves of 235 species of wild CMMR in Sichuan is about 36.72 million ton.There were 49 CMMR which have reserves beyond 100 thousand tons,such as Arisaematis rhizoma,Epimedii folium,Cimicifugae rhizoma,Acori tatarinowii rhizoma,Gentianae macrophyllae radix,Polygoni multiflori radix etc.④In 2021,there were 215 species of CMMR cultivated in Sichuan,the main species were Aurantii fructus,Chuanxiong rhizoma,Polygonati rhizome,Salviae miltiorrhizae radix et rhizome.The planting area was 8.17 million and the production was 1.26 million ton.⑤All 183 countries were found CMMR,the number of the species of CMMR in 30 countries exceeded 800,including 16 countries which had more than 1000 kinds of CMMR,such as Emeishan,Hongya,Muli etc.The total types of the CMMR(up 118.31%),the reserves of the wild CMMR(up 119 times)and the number of the counties(up 3 times)which had plenty of CMMR,showed a marked increase over the 3rd CMMRI.8 new species were found in the the 4th CMMRI,such as Codonopsis atriplicifolia,Tongoloa tagongensis,Allium xinlongense,etc.Conclusion The species,the reserves of the CMMR and the resource rich countries in Sichuan are the top 3 in China and Sichuan is worthy of the title of"Hometown of Traditional Chinese Medicine".The compositions and types of the family,genus and species of the CMMR in Sichuan have significantly increased.The basic information of the CMR in Sichuan was clearly found out during the 4th CMMRI,and beneficial for the sustainable development and utilization of the CMMR in Sichuan.

Objective To compare the changes of the medical animal resources(MAR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2020-2022).Methods After field investigation and identification of the photos of the animals,the data of the MAR in Sichuan found in the 4th CMMRI were analyzed and compared with the data of 3rd CMMRI.Results 745 species of MAR were found in Sichuan during the 4th CMMRI,including 212 families and 468 genera.Compared with the 108 species found in 3rd CMMRI,the number of MAR in Sichuan had greatly increased,The Aves was found to have 243 species of MAR,which is the most plenty one among the 7 classes.There were 14 families which have more than 10 species of MAR.The family,Cyprinidae had 48 species of MAR.There were 33 common Chinese medicinal herbs and 3 genuine medicinal materials including Cordyceps sinensis,musk and Venenum bufonis were found in this investigation.The new distributions of Liangshan Cordyceps and Cordyceps gunnii were found in the investigation,and the new resources of Atypus heterothecus was found in Mountain Emei.There were 140 species of key protection of wild medicinal animals,including 44 species of animals under first-class protection and 96 species of animals under second-class protection.There were 230 species of animals which had important ecological,scientific,and social values,too.Conclusion Sichuan was plenty of medical animal resources and the protection of the forest musk deer,the Cordyceps sinensis and the pangolin was need to be strengthened.